Background:This study evaluated the addition of sorafenib to gemcitabine and cisplatin in biliary adenocarcinoma first-line therapy.Methods:Patients with advanced biliary adenocarcinomas received gemcitabine 1000 mg m−2 and cisplatin 25 mg m−2 on a 2 weeks on/1 week off cycle and sorafenib 400 mg twice daily. After the initial 16 patients were enrolled, the chemotherapy doses were amended in view of grade 3 and 4 hand–foot skin reaction and haematologic toxicity. Subsequently, 21 patients received gemcitabine 800 mg m−2, cisplatin 20 mg m−2 and sorafenib 400 mg. The primary end point was an improvement in 6-month progression-free survival (PFS6) from historical 57–77% (90% power, type I error of 10%). Pretreatment pERK, evaluated by immunostaining, was correlated with clinical outcome.Results:A total of 39 patients were accrued. The most common grade 3–4 toxicities noted in >10% of patients were fatigue, elevated liver function tests and haematologic toxicities including thromboemboli, hyponatraemia and hypophosphataemia. Six-month progression-free survival was 51% (95% confidence interval (CI) 34–66%). Median PFS and overall survival were 6.5 (95% CI: 3.5–8.3) and 14.4 months (95% CI: 11.6–19.2 months), respectively. No correlation was observed between pERK and outcomes.Conclusion:The addition of sorafenib to gemcitabine and cisplatin in biliary adenocarcinomas did not improve efficacy over historical data, and toxicity was increased.

Background Although gemcitabine plus platinum chemotherapy is the established first‐line regimen for advanced biliary cancer (ABC), there is no standard second‐line therapy. This study evaluated current practice and outcomes for second‐line chemotherapy in patients with ABC across 3 US academic medical centers. Methods Institutional registries were reviewed to identify patients who had received second‐line chemotherapy for ABC from April 2010 to March 2015 along with their demographics, diagnoses and staging, treatment histories, and clinical outcomes. Overall survival from the initiation of second‐line chemotherapy (OS2) was estimated with Kaplan‐Meier methods. Results This study identified 198 patients with cholangiocarcinoma (intrahepatic [61.1%] or extrahepatic [14.1%]) or gallbladder carcinoma (24.8%); 52% received at least 3 lines of systemic chemotherapy. The median OS2 was 11 months (95% confidence interval [CI], 8.8‐13.1 months). The median OS2 for patients with intrahepatic cholangiocarcinoma was 13.4 months (95% CI, 10.7‐17.8 months), which was longer than that for patients with extrahepatic cholangiocarcinoma (6.8 months; 95% CI, 5‐10.6 months) or gallbladder carcinoma (9.4 months; 95% CI, 7.2‐12.3 months; P = .018). The median time to second‐line treatment failure was 2.2 months (95% CI, 1.8‐2.7 months), and it was similar across tumor locations (P = .60). Conclusions In this large cohort of patients with ABC treated across 3 academic medical centers after the failure of first‐line chemotherapy, the time to treatment failure on standard therapies was short, although the median OS2 was longer than has been reported previously, and more than half of the patients received additional lines of treatment. This multicenter collaboration represents the largest cohort studied to date of second‐line chemotherapy for ABC and provides a contemporary benchmark for future clinical trials.